As adult mammals lack the capacity to regenerate damaged neurons, dysfunction of the central nervous system (CNS) after brain injury or in neurodegenerative diseases increasingly impairs life quality in our aging society. Despite intensive research efforts, induction of regeneration and subsequent functional recovery of the injured mammalian CNS remains a challenge, which makes the search for new regeneration-inducing molecules essential. In this project we aim to shed light on how dendritic shrinkage/remodeling contributes to neuronal survival and axonal regeneration and to identify and further characterize molecules and pathways that contribute to neuroprotection and regeneration. Hereto, we will use state-of-theart molecular, biochemical, morphological, functional and behavioral tools in the visual system of two vertebrates with different strengths, zebrafish and mice. As zebrafish have a very high regenerative potential, they provide a unique model for the analysis and identification of crucial molecules and signaling pathways contributing to a successful axonal regeneration after CNS injury. Subsequent validation of our findings in mice allows the identification of key regulatory molecules for improved regeneration in mammals. This study proposes to advance our knowledge on the molecules and mechanisms underlying axonal outgrowth, which is highly needed to establish successful and novel regenerative therapies promoting neural repair.